Search

金沢大学大学院医学系研究科血管分子科学, Background: Although chemokines play an important role in various inflammatory diseases, there have been few studies about the role of chemokines in alopecia areata (AA). Objectives: To determine serum levels of chemokines in patients with AA and their clinical correlations. Methods: Serum samples from 85 patients with AA, 20 patients with atopic dermatitis, 20 patients with psoriasis vulgaris and 28 normal controls were examined by the cytometric bead array assay assessing monokine induced by interferon (IFN)-γ (MIG), RANTES, interleukin-8 (IL-8), IFN-inducible protein-10, monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)-1α, MIP-1β and eotaxin levels. Secreted chemokine levels from peripheral blood mononuclear cells (PBMC) of patients with AA were also investigated. Results: Serum MIG, RANTES, IL-8 and eotaxin levels were selectively increased in patients with AA compared with normal controls. Levels of MIG, RANTES and IL-8 secreted from PBMC of patients with AA were also increased. Furthermore, elevated serum MIG and RANTES levels significantly correlated with the disease activity. RANTES levels were nonsignificantly associated with a predisposition to atopy. Conclusions: These results suggest that MIG and RANTES play an important role in the development of AA and are useful as markers of disease activity and as therapeutic targets. © 2007 The Authors.全文公開200809

金沢大学大学院医学系研究科血管分子科学, Background: B cells have been demonstrated to have critical roles in developing autoimmune bullous diseases. Recently identified tumor necrosis factor-like molecules, B cell-activating factor of the TNF family (BAFF) and a proliferation-inducing ligand (APRIL) are essential molecules for B cell development, survival, and proliferation. Although the functions of APRIL have not been fully evaluated, recent studies suggest that circulating levels of APRIL are increased in various autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis. Objectives: To determine serum APRIL levels in patients with pemphigus vulgaris (PV) and bullous pemphigoid (BP), and compare those with clinical findings and laboratory findings. Patients/Methods: Sera from 15 PV patients, 43 BP patients, and 15 normal controls were subjected to ELISA assays to measure serum APRIL, BAFF, Dsg3, and BP180 levels. Results and conclusions: Circulating APRIL levels were significantly elevated in BP patients but not in PV patients, and correlated with serum BAFF levels. Our study revealed that serum APRIL levels tended to be increased in the quite early stage of disease. In conclusion, circulating APRIL levels may be a useful marker for early activation of autoimmune diathesis, and furthermore, an effective therapeutic target molecule in patients with BP. © 2007 Japanese Society for Investigative Dermatology.

Background: Autoimmune bullous diseases are characterized by autoantibodies against specific adhesion molecules of the skin and/or mucous membrane. While these autoantibodies are known to play a primary role in the disease manifestation, it remains unknown how disease-specific autoreactive B cells and autoantibodies are induced. Recent studies have indicated the importance of the CD40 and CD40 ligand (CD40L) receptor-ligand pair in the immunopathogenesis of autoimmune diseases. CD40L circulates in soluble form, and some reports suggest that serum soluble CD40L (sCD40L) levels are increased in various autoimmune diseases. Objectives: To determine serum sCD40L levels in patients with pemphigus vulgaris (PV) and bullous pemphigoid (BP), and to determine their correlation with clinical findings and laboratory findings. Patients and Methods: Sera from 10 PV patients, 35 BP patients and 12 normal controls were subjected to ELISA assays to measure serum levels of sCD40L, anti-desmoglein-3 antibody and anti-BP180 antibody. Results and Conclusions: Circulating sCD40L levels were significantly elevated in BP patients, but not in PV patients. Serum sCD40L levels increased in the early stage of disease onset and recurrence in BP patients. In conclusion, circulating sCD40L levels may be a useful marker for early activation of autoimmune diathesis and, furthermore, an effective therapeutic target in patients with BP.

Copyright © 2015, American Association for the Advancement of Science., The skin of an adult human contains about 20 billion memory T cells. Epithelial barrier tissues are infiltrated by a combination of resident and recirculating T cells in mice, but the relative proportions and functional activities of resident versus recirculating T cells have not been evaluated in human skin. We discriminated resident from recirculating T cells in human-engrafted mice and lymphoma patients using alemtuzumab, a medication that depletes recirculating T cells from skin, and then analyzed these T cell populations in healthy human skin. All nonrecirculating resident memory T cells (TRM) expressed CD69, but most were CD4(+), CD103(-), and located in the dermis, in contrast to studies in mice. Both CD4(+) and CD8(+) CD103(+) TRM were enriched in the epidermis, had potent effector functions, and had a limited proliferative capacity compared to CD103(-) TRM. TRM of both types had more potent effector functions than recirculating T cells. We observed two distinct populations of recirculating T cells, CCR7(+)/L-selectin(+) central memory T cells (TCM) and CCR7(+)/L-selectin(-) T cells, which we term migratory memory T cells (TMM). Circulating skin-tropic TMM were intermediate in cytokine production between TCM and effector memory T cells. In patients with cutaneous T cell lymphoma, malignant TCM and TMM induced distinct inflammatory skin lesions, and TMM were depleted more slowly from skin after alemtuzumab, suggesting that TMM may recirculate more slowly. In summary, human skin is protected by four functionally distinct populations of T cells, two resident and two recirculating, with differing territories of migration and distinct functional activities., This work was supported by a generous charitable contribution from Edward P. Lawrence, Esq., R01 AR063962 NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (to R.A.C.), R01 AR056720 NIH/NIAMS (to R.A.C.), a Damon Runyon Clinical Investigator Award (to R.A.C.), the SPORE in Skin Cancer P50 CA9368305 NIH/National Cancer Institute (to T.S.K.), and R01 AI097128 National Institute of Allergy and Infectious Diseases (to T.S.K. and R.A.C.).

Although anti-Fcgamma receptor antibodies (Abs) are detected in various autoimmune diseases, there have been no studies about the anti-Fcgamma receptor Abs in alopecia areata (AA). To detect the anti-Fcgamma receptor Abs in patients with AA and their clinical correlations, Serum samples from 72 patients with AA and 23 normal controls were examined by enzyme-linked immunosorbent assay assessing anti-Fcgamma receptor Ab levels. Anti-Fcgamma receptor I Abs were significantly frequently detected in patients with AA compared with normal controls. Furthermore, the detection of anti-Fcgamma receptor I Abs significantly inversely correlated with the disease duration. These results suggest that anti-Fcgamma receptor I Ab and Fcgamma receptor I play an important role in the regulation of AA, are useful for a marker of the disease prognosis and are worth intense research for the reasonable and specific therapy of AA.

We report two cases of lymphocytoma cutis caused by pierced earrings, with the results of patch tests and X-ray microanalyses on electron microscopy. We detected zinc through scanning electron microscopy from the specimen of Case 1 and gold and titanium through transmission electron microscopy from Case 2. This is the first report to demonstrate the presence of metal fragments in the lesion, which may suggest the remanence of metal for 20 years, bringing about persistent allergic reaction.

Summary Background BAFF [B-cell activating factor belonging to the tumour necrosis factor (TNF) family] is a member of the TNF superfamily that regulates B-lymphocyte proliferation and survival. It has been demonstrated that increased levels of soluble BAFF are associated with systemic autoimmunity in patients with systemic lupus erythematosus, rheumatoid arthritis and Sjogren's syndrome, and in animal models of spontaneous autoimmune diseases. However, the significance of circulating BAFF in autoimmune bullous diseases is unknown. Objectives To examine whether BAFF levels are elevated in the autoimmune blistering diseases pemphigus vulgaris (PV) and bullous pemphigoid (BP). Methods We examined sera obtained from 21 patients with PV, 39 patients with BP and 22 healthy donors. We performed enzyme-linked immunosorbent assays for soluble BAFF and each disease-specific antibody: antidesmoglein-3 antibody for PV and anti-BP180 antibody for BP. Results Significant elevations of serum BAFF levels were found in the patients with BP, but not with PV. There was apparently no significant association between the serum BAFF levels and titres of anti-BP180 antibodies in the patients with BP. However, serum BAFF levels tended to be more elevated in patients with a shorter disease duration. There was a tendency that BAFF levels increased before the anti-BP180 antibody levels increased at the onset of BP and quickly decreased in response to treatment. Conclusions BAFF may be a useful marker for early activation of an autoimmune diathesis and may play a critical role in triggering activation of self-antigen-driven autoreactive B cells in BP.

Background Treatments of port-wine stains with conventional pulsed dye laser yield inconsistent results. Objective We evaluated the efficacy and safety of the longer pulse duration 595-nm dye laser. Methods Sixty-six adult Japanese patients were enrolled in this prospective study. The laser treatment with a cooling device was repeated 4 times at 8-week intervals with a consistent setting of 10-ms pulse duration and an energy fluence of 12 J/cm 2 , using 7-mm spot size. Results Improvement of port-wine stains was observed after multiple treatments, and 67% of the patients achieved either good or excellent response after the fourth treatment. Transient purpura, edema, or both were noted immediately after each treatment (76%-79% and 58%-67%, respectively). Hyperpigmentation (8%-17%) and hypopigmentation (6%-14%) were also mild and their occurrence did not increase by repeating treatments. Limitations Eighty five percent of the patients were classified as having Fitzpatrick skin type IV. Conclusion Our study indicated that the 595-nm dye laser with 10-ms pulse duration may be effective and well tolerated in the treatment of port-wine stains in adult Asians.

Cell surface molecules on lymphocytes positively or negatively modulate the Ag receptor signaling, and thus regulate the fate of the cell. CD22 is a B cell-specific cell surface protein that contains multiple ITIMs in the cytoplasmic tail, and critically regulates B cell activation and survival. CD22 regulation on B cell signaling is complex because CD22 can have both positive and negative roles in various contexts. We generated phosphospecific polyclonal Abs reacting four major CD22 tyrosine motifs (Y762, Y807, Y822, and Y842) and analyzed the pattern and intensity of phosphorylation of these tyrosine residues. The tyrosine motifs, Y762, Y822, and Y842, are considered as ITIM, whereas the other, Y807, is suggested to be important for Grb2 recruitment. Approximately 10% of the four tyrosine residues were constitutively phosphorylated. Upon anti-IgM ligation, CD22 Y762 underwent most rapid phosphorylation, whereas all four tyrosine residues were eventually phosphorylated equally at ∼35% of all CD22 molecules in the cell. By contrast, anti-CD40 stimulation specifically up-regulated anti-IgM-induced phosphorylation of tyrosines within two ITIM motifs, Y762 and Y842, which was consistent with in vivo finding of the negative role of CD22 in CD40 signaling. Thus, CD22 phosphorylation is not only quantitatively but also qualitatively regulated by different stimulations, which may determine the outcome of B cell signaling.

Drug-induced hypersensitivity syndrome (DIHS) is a rare but severe disease with multiorgan failure. Recently, the association of the human herpesvirus (HHV) family, particularly of HHV-6, with DIHS has been reported. We report a 43-year-old female diagnosed as having DIHS based on the clinical course and laboratory examinations. The HHV-6 reactivation was demonstrated by significantly increased levels of the specific antibody in her paired sera and by polymerase chain reaction of HHV-6 DNA. Notably, transient hypogammaglobulinaemia was detected in the early stage of the disease, which was associated with the disease activity. By contrast, the serum IgE level and eosinophils were increased 2 or 3 weeks later. In addition, serum levels of interferon γ, interleukin (IL)-4 and soluble IL-2 receptor, which were increased in the early phase of the disease, decreased gradually after the corticosteroid therapy.

T helper type 9 (TH9) cells can mediate tumor immunity and participate in autoimmune and allergic inflammation in mice, but little is known about the TH9 cells that develop in vivo in humans. We isolated T cells from human blood and tissues and found that most memory TH9 cells were skin-tropic or skin-resident. Human TH9 cells coexpressed tumor necrosis factor-α and granzyme B and lacked coproduction of TH1/TH2/TH17 cytokines, and many were specific for Candida albicans. Interleukin-9 (IL-9) production was transient and preceded the up-regulation of other inflammatory cytokines. Blocking studies demonstrated that IL-9 was required for maximal production of interferon-γ, IL-9, IL-13, and IL-17 by skin-tropic T cells. IL-9-producing T cells were increased in the skin lesions of psoriasis, suggesting that these cells may contribute to human inflammatory skin disease. Our results indicate that human TH9 cells are a discrete T cell subset, many are tropic for the skin, and although they may function normally to protect against extracellular pathogens, aberrant activation of these cells may contribute to inflammatory diseases of the skin.

In cosmetic clinical practice, many patients express the desire for removal of melanocytic nevi, especially those on the face. The carbon dioxide (CO2) laser currently is the preferred for treatment of such lesions because of less scar formation, less bleeding, and simplicity of the procedure. However, if the diameter of the lesion is greater than 5 mm, many clinicians prefer surgical resection to laser resection because laser resection of relatively large nevi often results in the formation of a conspicuous dimple. The authors developed a serial laser excision method for melanocytic nevi larger than 5 mm, with division of the lesion into multiple segments, which allowed the ablated area to gain optimal granulation and reepithelialization, leading to a satisfactory cosmetic appearance. This novel procedure was performed for 25 patients with melanocytic nevi ranging from 5 to 10 mm in diameter. The lesions were divided into two segments in 21 patients, three segments in 3 patients, and four segments in 1 patient. The divided parts of the lesions were ablated by CO2 laser serially at intervals of 2–4 weeks. All the patients obtained optimal granulation and epithelialization in the treated lesions, and the final appearance was satisfactory. Although the therapeutic period was longer than for a surgical excision or a single laser treatment, the new treatment approach of serial excision by CO2 laser achieved favorable outcomes for the treatment of relatively large nevi 5–10 mm in size. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Lon ATP-dependent protease plays an important role in regulating many biological processes in bacteria. In this study, we examined the organic solvent tolerance of a Δlon mutant of Escherichia coli K-12 and found that the mutant showed remarkably higher organic solvent tolerance than the parent strain. Δlon mutants are known to overproduce capsular polysaccharide, resulting in the formation of mucoid colonies. We considered that this increase in capsular polysaccharide production might be involved in the organic solvent tolerance in E. coli. However, a ΔlonΔwcaJ double-gene mutant displaying a nonmucoid phenotype was as tolerant to organic solvents as the Δlon mutant, suggesting that capsular polysaccharide is not involved in organic solvent tolerance. On the other hand, the Lon protease is known to exhibit proteolytic activity against the transcriptional activators MarA and SoxS, which can enhance the expression level of the AcrAB-TolC efflux pump. We found that the Δlon mutant showed a higher expression level of AcrB than the parent strain. In addition, the ΔlonΔacrB double-gene mutant showed a significant decrease in organic solvent tolerance. Thus, it was shown that organic solvent tolerance in the Δlon mutant depends on the AcrAB-TolC pump but not capsular polysaccharide. E. coli strain JA300 acrRIS marR overexpresses the AcrAB-TolC pump and exhibits high-level solvent tolerance. In an attempt to further improve the solvent tolerance of JA300 acrRIS marR, a lon gene disruptant of this strain was constructed. However, the resulting mutant JA300 acrRIS marR Δlon showed lower solvent tolerance than JA300 acrRIS marR.

Cutaneous T cell lymphoma (CTCL) is a cancer of skin-homing T cells with variants that include leukemic CTCL (L-CTCL), a malignancy of central memory T cells (T(CM)), and mycosis fungoides (MF), a malignancy of skin resident effector memory T cells (T(EM)). We report that low-dose alemtuzumab (αCD52) effectively treated patients with refractory L-CTCL but not MF. Alemtuzumab depleted all T cells in blood and depleted both benign and malignant T(CM) from skin, but a diverse population of skin resident T(EM) remained in skin after therapy. T cell depletion with alemtuzumab required the presence of neutrophils, a cell type frequent in blood but rare in normal skin. These data suggest that T(CM) were depleted because they recirculate between the blood and the skin, whereas skin resident T(EM) were spared because they are sessile and non-recirculating. After alemtuzumab treatment, skin T cells produced lower amounts of interleukin-4 and higher amounts of interferon-γ. Moreover, there was a marked lack of infections in alemtuzumab-treated L-CTCL patients despite the complete absence of T cells in the blood, suggesting that skin resident T(EM) can protect the skin from pathogens even in the absence of T cell recruitment from the circulation. Together, these data suggest that alemtuzumab may treat refractory L-CTCL without severely compromising the immune response to infection by depleting circulating T(CM) but sparing the skin resident T(EM) that provide local immune protection of the skin.

We report a patient with herpetiform pemphigus who was negative for autoantibodies to desmoglein (Dsg)1 or 3. He had erythemas with vesicles lining the margins on the trunk and extremities. Histopathology revealed intraepidermal blister with prominent eosinophil infiltration. Direct and indirect immunofluorescence demonstrated the presence of depositing and circulating immunoglobulin (Ig)G autoantibodies, but no IgA antibodies, to keratinocyte cell surface. Nonetheless, neither anti-Dsg1 nor Dsg3 antibodies were detected by enzyme-linked immunosorbent assay. Immunoblotting using human epidermal extracts also showed no reactivity with known intraepidermal or epidermal-dermal junctional substances. Immunoelectronmicroscopy revealed the reactivity on the portion of keratinocyte cell surface but not on the desmosomes. This case suggests that non-desmoglein antigen on keratinocyte cell surface can be targeted in some patients with this unusual variant of pemphigus.

Delineating the relative contributions of B lymphocytes during the course of autoimmune disease has been difficult. Therefore, the effects of depleting all mature B cells using a potent CD20 mAb, or of depleting circulating and marginal zone B cells using a ligand-blocking CD22 mAb, were compared in NZB/W F1 mice, a model for human systemic lupus erythematosus. Single low-dose mAb treatments depleted B cells efficiently in both NZB/W F1 and C57BL/6 mice. Prophylactic B cell depletion by repeated CD20 mAb treatments prolonged survival during pristane-accelerated lupus in NZB/W F1 mice, whereas CD22 mAb had little effect. Despite effective B cell depletion, neither mAb treatment prevented autoantibody generation. In addition, CD20, CD22, and control mAb-treated NZB/W F1 mice developed anti-mouse IgG autoantibodies in contrast to parental NZB and NZW strains, which may have reduced the effectiveness of B cell depletion. Despite this, low-dose CD20 mAb treatment initiated in 12–28-wk-old mice, and administered every 4 wk thereafter, significantly delayed spontaneous disease in NZB/W F1 mice. By contrast, B cell depletion initiated in 4-wk-old mice hastened disease onset, which paralleled depletion of the IL-10–producing regulatory B cell subset called B10 cells. B10 cells were phenotypically similar in NZB/W F1 and C57BL/6 mice, but were expanded significantly in young NZB/W F1 mice. Thus, B cell depletion had significant effects on NZB/W F1 mouse survival that were dependent on the timing of treatment initiation. Therefore, distinct B cell populations can have opposing protective and pathogenic roles during lupus progression.

Although contact hypersensitivity (CHS) has been considered a prototype of T cell-mediated immune reactions, recently a significant contribution of regulatory B cell subsets in the suppression of CHS has been demonstrated. CD22, one of the sialic acid-binding immunoglobulin-like lectins, is a B cell-specific molecule that negatively regulates BCR signaling. To clarify the roles of B cells in CHS, CHS in CD22−/− mice was investigated. CD22−/− mice showed delayed recovery from CHS reactions compared with that of wild-type mice. Transfer of wild-type peritoneal B-1a cells reversed the prolonged CHS reaction seen in CD22−/− mice, and this was blocked by the simultaneous injection with IL-10 receptor Ab. Although CD22−/− peritoneal B-1a cells were capable of producing IL-10 at wild-type levels, i.p. injection of differentially labeled wild-type/CD22−/− B cells demonstrated that a smaller number of CD22−/− B cells resided in lymphoid organs 5 d after CHS elicitation, suggesting a defect in survival or retention in activated CD22−/− peritoneal B-1 cells. Thus, our study reveals a regulatory role for peritoneal B-1a cells in CHS. Two distinct regulatory B cell subsets cooperatively inhibit CHS responses. Although splenic CD1dhiCD5+ B cells have a crucial role in suppressing the acute exacerbating phase of CHS, peritoneal B-1a cells are likely to suppress the late remission phase as “regulatory B cells.” CD22 deficiency results in disturbed CHS remission by impaired retention or survival of peritoneal B-1a cells that migrate into lymphoid organs.

The patient was a 74-year-old woman who was diagnosed with advanced breast cancer, T4aN0M0, stage IV. She was placed on chemotherapy of weekly paclitaxel (PTX) (60 mg/m(2) day 1, 8, 15 with 1 course consisting of 28 days). We used dexamethasone (8 mg/body) as premedication for chemotherapy every time. Three courses were performed with no severe adverse reaction. On the fourth course, day 8, she complained of nausea, vomiting, paroxysmal cough and fecal incontinence after a few minutes of dexamethasone administration. Her blood pressure dropped to a minimum of 64 mmHg (systolic pressure) and she soon became drowsy. We diagnosed the anaphylaxis-like reaction for dexamethasone, immediately discontinued dexamethasone infusion, and treated her successfully. Forty minutes after the episode had occurred, she recovered. The few reports on anaphylaxis or anaphylaxis-like reaction to dexamethasone must be taken into account when we use these drugs.

To determine the efficacy of ultrasonography for the diagnosis of subcutaneous benign lesions.Retrospective study.Tokyo Kousei-Nenkin Hospital, Tokyo, Japan. Patients The study included 183 patients with subcutaneous benign lesions who underwent ultrasonography and then received a pathologic diagnosis after surgery.The study evaluated the number of cases in which the preoperative diagnosis after ultrasonography or just after palpation agreed with the pathologic diagnosis.Ultrasonography significantly increased the preoperative diagnostic yield of subcutaneous benign lesions (after palpation, 29%; after ultrasonography, 46%; P.001). The sensitivity for the diagnosis of lipoma (after palpation, 54.8%; after ultrasonography, 88.1%; P.01) and the specificity for the diagnosis of epidermal cyst (after palpation, 93.5%; after ultrasonography, 99.3%; P.05) significantly increased after ultrasonography. The sensitivity for the diagnosis of epidermal cyst and ganglion also tended to increase after ultrasonography. Conclusion The study results suggest that ultrasonography is useful for the preoperative examination of subcutaneous benign lesions.

Contact hypersensitivity (CHS) is a cutaneous immune reaction mediated mainly by antigen-specific effector T cells and is regarded as a model for Th1/Tc1-mediated inflammation. However, recent reports have suggested pivotal roles of B cells in CHS. CD19 serves as a positive B-cell response regulator that defines signaling thresholds critical for B-cell responses. In the current study, we assessed the role of the B-cell-specific surface molecule CD19 on the development of CHS by examining CD19-deficient mice. Although CD19-deficient mice are hyposensitive to a variety of transmembrane signals, CD19 loss resulted in increased and prolonged reaction of CHS, suggesting an inhibitory role of CD19 expression in CHS. Sensitized lymph nodes and elicited ear lesions from CD19-deficient mice exhibited Th1/Tc1-shifted cytokine profile with increased interferon-gamma expression and decreased interleukin-10 expression. Adoptive transfer experiments revealed that CD19 expression in recipient mice was required for optimal suppression of CHS response, indicating its role in the elicitation phase. Furthermore, spleen B cells, especially marginal zone B cells, from wild-type mice were able to normalize exaggerated CHS reactions in CD19-deficient mice. Thus, CD19 expression in B cells is critical for termination of CHS responses, possibly through the function of regulatory B cells.

Background Tear trough deformity is a primary complaint in those who believe it causes an old and tired appearance. This deformity naturally increases with aging, but there are younger people that also complain about the appearance of their lower eyelid area. Recently, many authors have reported good results treating this deformity with transconjunctival orbital fat repositioning. Although Kawamoto has pointed out a possible need for a procedure modification in Asians with a brachycephalic face, thus far, there have been no reports evaluating such procedures in Asians. Objective In November 2004, to validate past clinical experiences, we planned a prospective study in young Japanese Asians to assess the efficacy of orbital fat repositioning for improvement of lower eyelid disfigurement. Our goal was to evaluate the viability of transconjunctival repositioning of orbital fat using a preseptal dissection and supraperiosteal pocket method. Methods The prospective study was performed in 20 Japanese patients younger than 40 years of age who were referred to our department over a 1-year period. These patients, in whom eyelid skin tightening was deemed unnecessary, underwent transconjunctival blepharoplasty. Using a transconjunctival incision, a preseptal dissection was performed, extending over the arcus marginalis. A supraperiosteal pocket was made below the orbicularis oculi muscle with blunt scissor dissection. The arcus marginalis was then released by cautery cutting. Both the orbital fat and orbital septum were anchored across the orbital rim with 5-0 polyglactin sutures. Results Results in 18 of 20 patients (90%) were rated as “excellent,” the result for 1 patient (5%) was rated as “good,” and the result for the 1 remaining patient was rated as “fair.” No major eye or eyelid complications, such as lower eyelid retraction, ectropion, or diplopia, were observed. Conclusions Transconjunctival orbital fat repositioning (incorporating preseptal dissection and supraperiosteal pockets) is an effective and safe method for relatively young Asians complaining of lower eyelid disfigurement.

We have recently used Q-switched alexandrite laser for the treatment of various kinds of pigmented skin lesions. We retrospectively compared therapeutic outcomes of 153 Japanese patients who consulted our department. This approach was not very efficient for nevus spilus/cafe-au-lait spots, which seemed laser-resistant, especially when the pigmentation had appeared after 1 year of age, was treated after 5 years of age, was located on the face, was oval with a smooth border, and the patient was male. This approach was equally effective for senile lentigo, nevus of Ota, and Mongolian spots, but less effective for acquired bilateral nevus of Ota-like macules. Some patients with sacral Mongolian spots or those with light-colored, senile lentigo developed severe post-inflammatory hyperpigmentation after treatment. As a whole, good therapeutic outcome was achieved after multiple treatment sessions. However, the use of other lasers or other treatment modalities should be considered to treat nevus spilus/cafe-au-lait spots.

We report the case of a 55-year-old female with bullous pemphigoid (BP) who was positive for anti-BP180 and anti-laminin 5 antibodies after development of graft-vs-host disease (GVHD) caused by a bone marrow transplant. She had tense blisters on her trunk and extremities. Histologic examination showed a subepidermal blister and marked lymphocytic infiltration, especially eosinophils. Direct immunofluorescence revealed a linear deposition of IgG on the base membrane zone. Indirect immunofluorescence on 1M NaCl split skin revealed a linear IgG deposition to both sides of the epidermal and the dermal layers. Immunoblot assays using human epidermal extracts and BP180 NC16a domain recombinant protein confirmed the presence of IgG antibodies against BP180 and recombinant BP180 NC16a domain protein. Furthermore, immunoblotting using laminin 5 purified from human keratinocyte extract as the substrate demonstrated reactivity against the gamma2 and beta3 subunits but not the alpha3 subunit of laminin 5. We diagnosed BP and treated her with prednisolone (40 mg/day). Both skin and oral lesions resolved without leaving scars on the bulla. Immune disturbance as well as destruction of basal epidermal cells and base membrane by GVHD may result in the induction of autoimmune blistering diseases with unusual clinical and laboratory manifestations.

BACKGROUND As Bayoumi, et al pointed out in their article (J. Natl. Cancer Inst. 2000, vol 92, p 1731), it is evident that treatment of prostate cancer with Luteinizing Hormone Releasing Hormone (LHRH) analogue costs more than treatment by bilateral orchiectomy. However, patients with metastatic prostate cancer are usually treated with LHRH analogue. Does this mean that urologist choose higher cost and less Quality-Adjusted Life Year (QALY) treatment? Therefore, we urologists should re-analyze their conclusion whether the treatment with LHRH analogue is really strictly dominated (high cost and low effect). MATERIAL AND METHOD We performed a cost-utility analysis using the Markov model based on a formal meta-analysis and literature review, using the same assumptions as Bayoumi, et al, from the perspective of insurer. The base case was assumed to be a 65-year-old man with symptomatic metastatic prostate cancer. The model used time horizon of 10 years. Five androgen ablation therapies were evaluated as first-line therapy: diethylstilbestrol diphosphate (DES), orchiectomy, orchiectomy + nonsteroidal antiandrogen (NSAA), LHRH analogue and LHRH analogue + NSAA. Outcome measures were QALY, lifetime costs and incremental cost-effectiveness ratios. RESULTS While DES was the least expensive therapy with the lowest QALY, LHRH analogue monotherapy was the second most expensive therapy with the longest QALY. Incremental cost-effectiveness ratios relative to DES of LHRH (yen 4,288,295/QALY) was cheaper than that of orchiectomy when quality of life (QOL) weight of orchiectomy was assumed to be 0.94 relative to that of LHRH analogue. Contrarily, LHRH analogue + NSAA is excluded with strict dominance and Orchiectomy + NSAA is excluded with extended dominance. CONCLUSION Although LHRH analogue costs higher than orchiectomy, LHRH analogue can offer longer QALY than orchiectomy. Cost/QALY of LHRH analogue relative to DES is yen 4,288,295/QALY, which we considered to represent a good value. Choice of therapy depends on the patient's preference.

This paper documents an analysis of the impact of respirator use on medical expenses with observational data based on medical records from all over Japan.The data set included records of medical procedures during a single month, but not for procedures and information extending over plural months. Accordingly, censoring was an important problem. To overcome this, samples are classified into four groups; complete, right censoring, left censoring and both censoring ones using length of respirator use and hospital stay. Then, the Gompertz model was applied to calculate the expected length of respirator use. Simultaneously, medical expenses for respirator use were also estimated.The estimated expected length of respirator use was from 10 to 104 days, with expected medical expenses per case of from 30,000 to 40,000 yen and the number of respirator usages on aggregate of 5510.This means the impact of respirator use on medical expenses is from 18 to 250 billion yen per year.

To the editor Low dose alemtuzumab (LDA) is a highly effective and generally well tolerated therapy for refractory cutaneous T cell lymphoma (CTCL) patients with peripheral blood disease.1 LDA is effective in patients with blood involvement (leukemic disease) but ineffective in MF, reflecting the fact that these lymphomas derive from distinct T-cell subsets. Malignant T cells in patients with blood disease have the phenotype of CCR7+/L-selectin+ central memory cells (TCM), migratory cells that recirculate between skin, blood and lymph nodes whereas MF T cells are derived from non-migratory skin resident memory T cells (TRM).2 Because the mechanism of T cell depletion with LDA requires neutrophils and/or NK cells, cells frequent in blood but rare in skin, LDA kills T cells in blood but not in skin.1 In patients with blood disease, LDA depletes all circulating T cells and purges the skin over time of recirculating malignant T cells, leading to complete and often durable remissions in 50% of patients while sparing benign T cells in skin.1 We present here our findings that clinical appearance can be used to discriminate patients likely to experience a complete remission following LDA from those that will have persistent and/or worsening skin disease.

The AcrAB-TolC efflux pump is involved in maintaining intrinsic organic solvent tolerance in Escherichia coli. Mutations in regulatory genes such as marR, soxR, and acrR are known to increase the expression level of the AcrAB-TolC pump. To identify these mutations in organic solvent tolerant E. coli, eight cyclohexane-tolerant E. coli JA300 mutants were isolated and examined by DNA sequencing for mutations in marR, soxR, and acrR. Every mutant carried a mutation in either marR or acrR. Among all mutants, strain CH7 carrying a nonsense mutation in marR (named marR109) and an insertion of IS5 in acrR, exhibited the highest organic solvent-tolerance levels. To clarify the involvement of these mutations in improving organic solvent tolerance, they were introduced into the E. coli JA300 chromosome by site-directed mutagenesis using λ red-mediated homologous recombination. Consequently, JA300 mutants carrying acrR::IS5, marR109, or both were constructed and named JA300 acrR IS, JA300 marR, or JA300 acrR IS marR, respectively. The organic solvent tolerance levels of these mutants were increased in the following order: JA300